Book/Report/Dissertation / PhD Thesis

FZJ-2017-04448

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Entwicklung stabiler Mn-Komplexe für die multimodale MR/PET-Bildgebung

Brandt, M. R. (Corresponding author)FZJ*

2017
Forschungszentrum Jülich GmbH Zentralbibliothek, Verlag Jülich

Please use a persistent id in citations: http://hdl.handle.net/2128/15100

Report No.: Juel-4400

Abstract: Different derivatives of the polyaminocarboxylate ligand $\textit{trans}$-cyclohexyldiaminotetraacetic acid(CDTA) were synthesized to evaluate isotopically radiolabelled manganese-based bimodal contrast agents for hybrid positron emission tomography/magnetic resonance (PET/MR) imaging. First, a bifunctional chelating agent precursor was synthesized in five steps, which can be coupled to a small and rigid central scaffold to obtain a multimeric manganese (II) chelating unit. For this purpose, phosphazene, adamantane, triazine and benzene scaffolds were evaluated. With phosphazene, adamantane and triazine, the synthesis of multimeric ligands was unsuccessful. When trisacetylenebenzene derivatives were used as central units, 1,3-dipolar cycloaddition with the azido-functionalized prochelator allowed obtaining a valeric acid functionalized and an unfunctionalised tristriazole-CDTA ligand (TTB-(CDTA)$_{3}$). Radiolabelling of these ligands with the positron emitting nuclide manganese-52g was first tested using commercially available CDTA, which could be successfully labelled within 30 min at room temperature. Using the non-active reference compound, a Reversed-Phase High Performance Liquid Chromatography (RP-HPLC) method was established for purification and identification of the radioactive compound [$^{52g}$Mn][Mn(CDTA)]$^{-2}$. The purified complex was incubated in human blood serum to quantify the dissociation behaviour of the radiocomplex under $\textit{in vivo}$ conditions. Size-Exclusion-HPLC allowed the determination of t$_{Diss1/2}$ = 12 h at 37 °C. Applying the established radiolabelling protocol, the TTB-(CDTA)$_{3}$-structures were successfully radiolabelled under the same conditions as before. A suitable HPLC purification method was developed using the inactive reference compounds. Relaxivity measurements performed on the unfunctionalized,trimeric manganese-CDTA-complex showed that coupling of three paramagnetic centers to asmall and rigid scaffold significantly enhances the longitudinal relaxivity (r$_{1}$ = 8.8 mmol$^{-1}$s$^{-1}$ at 20 MHz, 25 °C) as compared to unfunctionalised manganese-CDTA. Having also synthesized a valeric acid functionalised trimeric CDTA-ligand, isotopically radiolabelled manganese-based bimodal PET/MR probes with high relaxivity, stability and possible targeting properties are within reach.

Note: Univ. Köln, Diss., 2017

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Contributing Institute(s):

1. Nuklearchemie (INM-5)

Research Program(s):

1. 573 - Neuroimaging (POF3-573) (POF3-573)

Appears in the scientific report 2017

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Database coverage:
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